Alpha 1-adrenergic receptors and stimulation of [3H]inositol metabolism in rat brain: regional distribution and parallel inactivation.

The relationship between norepinephrine-stimulated phosphatidyl-inositol metabolism and alpha 1-adrenergic receptor density was examined in rat brain. Increases in phosphatidyl-inositol metabolism were determined by accumulation of [3H]inositol phosphates in the presence of lithium in brain slices, while receptor density was determined by specific binding of 125I-BE 2254 (125IBE) in membrane fractions. Treatment of slices of cerebral cortex with increasing concentrations of the irreversible alpha 1-adrenergic receptor antagonist phenoxybenzamine caused a parallel inactivation of specific 125IBE binding sites and norepinephrine-induced [3H]inositol phosphate accumulation, although approximately 20% of the binding sites remained after abolition of the inositol response. Comparison of the density of 125IBE binding sites and the magnitude of norepinephrine-stimulated [3H]inositol phosphate accumulation in 8 different brain regions did not show a particularly good correlation. The thalamus had the highest density of binding sites and an intermediate inositol response, while the hippocampus had the highest inositol response but an intermediate density of binding sites. However, the cerebellum had the lowest density of binding sites and no measurable inositol response. Treatment of slices of each region with 300 nM phenoxybenzamine abolished the inositol response and caused a 59-73% decrease in the density of 125IBE binding sites. The lack of correlation between receptor density and inositol response between brain regions could not be explained on the basis of receptor affinity, spare receptors, protein content, nor differences in slice size.(ABSTRACT TRUNCATED AT 250 WORDS)